Origin of Oligodendrocytes within the Human Spinal Cord

Abstract

To determine the time and site of origin of the oligodendrocyte lineage in the developing human spinal cord, we have examined tissues from 45 to 83 d postconception (dpc) using sets of probes and antibodies recognizing oligodendrocyte-specific glycolipids, transcripts, and proteins. We found that two clusters of oligodendrocyte precursors appear on or before 45 dpc on each side of the cord ventral ependyma above the floor plate. These precursors express glycolipids recognized by the O4 and Rmab antibodies, platelet-derived growth factor ␣-receptor, myelin basic protein (MBP), and 2Ј, 3Ј-cyclic nucleotide 3Ј phosphodiesterase as well as MBP and proteolipid transcripts. Expression of the morphogen sonic hedgehog was detected in the floor plate at 45 dpc and decreased at 58 dpc. During this period, oligodendrocyte precursors emerged in the ventral and lateral region of the forming white matter, a process occurring first in cervical and later in lumbar cord. The majority of O4 ϩ cells express the proliferating cell nuclear antigen (PCNA), and their pattern of dispersion suggests that these cells progressively populate the lateral and dorsal cord regions. Oligodendrocytes expressing galactocerebroside appeared at 53 dpc and did not express PCNA. Oligodendrocyte precursors were detected in dorsal cord regions at 74 dpc and at 83 dpc when myelination started in the ventral roots. Thus, oligodendrocyte precursors expressing myelin transcripts and proteins emerge in the ventral region of the embryonic cord several weeks before myelination.

Late Oligodendrocyte Progenitors Coincide with the Developmental Window of Vulnerability for Human Perinatal White Matter Injury

“…Despite the morphological diversity of human pre-OLs, their immunohistochemical phenotype identified them as oligodendroglial in origin and distinct from astroglia, resting or reactive microglia, and neuronal precursors. Restricted foci of O4-positive progenitors were detected in the ventral ventricular zone of the human spinal cord as early as 6 weeks (Hajihosseini et al, 1996). In agreement with most (Levine et al, 1993;Nishiyama et al, 1997;Reynolds and Hardy, 1997;Chang et al, 2000) but not all (Pouly et al, 1999) studies, our results in developing human brain also indicate that NG2 is specific to the OL lineage in vivo.…”

“…We also did not observe migratory streams of OL progenitors, but rather pre-OLs were diffusely distributed throughout the white matter by 18 weeks. In contrast to the rodent spinal cord (for review, see Hardy, 1997), in which the migration of OL progenitors occurs at midgestation, O4ϩ progenitors migrate from the human ventral ventricular zone of the cord considerably earlier between 6 and 8 weeks (Hajihosseini et al, 1996). NG2ϩ OL progenitors are abundant in the adult rat and human brain (Levine et al, 1993;Nishiyama et al, 1996Nishiyama et al, , 1997Reynolds and Hardy, 1997;Ong and Levine, 1999;Chang et al, 2000).…”

Identification of molecular subtypes of glioblastoma by gene expression profiling

“…In contrast to the 12q13-15+ GBMs, the EGFR-overexpressing GBMs expressed elevated levels of cyclin D2 (two fold increase, P ¼ 0.03; Table 1). The 12q13-15-upregulated GBMs were also significant for high levels of transcription of oligodendroglial genes (MBP, MAG, PLP1, Nkx2.2, Mal and Sox10) (Hajihosseini et al, 1996;Landry et al, 1997;Zhou et al, 2001;Fu et al, 2002). (Table 1).…”

“…12q13-15+ tumors were remarkable for upregulation of oligodendroglial genes, including MAG, MBP, PLP1, Nkx2.2, Sox10, Mal and 2 0 ,3 0 -cyclic nucleotide 3 0 , phosphodiesterase-3-CNP (Hajihosseini et al, 1996;Landry et al, 1997;Zhou et al, 2001;Fu et al, 2002). Morphologically, these tumors were GBMs, not oligodendrogliomas or mixed gliomas, and they contained equal level of GFAP transcripts relative to the non-12q13-15+ tumors.…”

Nogo and Nogo‐66 receptor in human and chick: Implications for development and regeneration

“…Whereas in adult rodent CNS Nogo-A is localized primarily in oligodendrocytes (Chen et al, 2000), during early development Nogo is associated with neurons. The onset of oligodendrocyte development in the chick and human has been previously determined by O4 immunostaining and occurs around E5-E6 in the chick and around 45 days of gestation in humans, whereas the onset of myelination is observed around E12 in chick and 20 weeks of gestation in humans (Ono et al, 1995;Tanaka et al, 1995;Hajihosseini et al, 1996;Grever et al, 1997). In this study, we have shown that, in the chick spinal cord, both Nogo-A transcript and protein can be detected at E3, a time when motor neurons are being generated and axon outgrowth begins, well before the onset of O4 expression.…”